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An Orphan No More?

Nuclear receptors are a superfamily of proteins that function as ligand-activated transcription factors. Among these proteins are the so-called "orphan receptors," such as the retinoid X receptor (RXR), for which the endogenous activating ligands have not been identified. Using a cell-based screening assay, Mata de Urquiza et al. show that docosahexaenoic acid (DHA), an abundant polyunsaturated fatty acid in mammalian brain, is a potent activator of RXR. DHA deficiency has previously been linked to defects in spatial learning capacity in rodents. The new data raise the possibility that DHA's effects are mediated through an RXR signaling pathway.